Engineering glucose metabolism of escherichia coli under nitrogen starvation

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

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  • Author: Chubukov, Victor

    University of California at Berkeley, United States

  • Author: Desmarais, John James

    University of California at Berkeley, United States

  • Author: Wang, George

    University of California at Berkeley, United States

  • Author: Chan, Leanne Jade G.

    University of California at Berkeley, United States

  • Author: Baidoo, Edward E. K.

    University of California at Berkeley, United States

  • Author: J. Petzold, Christopher

    University of California at Berkeley, United States

  • Author: Keasling, Jay D.

    Synthetic Biology Tools for Yeast, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970, Hørsholm, Denmark

  • Author: Mukhopadhyay, Aindrila

    University of California at Berkeley, United States

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A major aspect of microbial metabolic engineering is the development of chassis hosts that have favorable global metabolic phenotypes, and can be further engineered to produce a variety of compounds. In this work, we focus on the problem of decoupling growth and production in the model bacterium Escherichia coli, and in particular on the maintenance of active metabolism during nitrogen-limited stationary phase. We find that by overexpressing the enzyme PtsI, a component of the glucose uptake system that is inhibited by α-ketoglutarate during nitrogen limitation, we are able to achieve a fourfold increase in metabolic rates. Alternative systems were also tested: chimeric PtsI proteins hypothesized to be insensitive to α-ketoglutarate did not improve metabolic rates under the conditions tested, whereas systems based on the galactose permease GalP suffered from energy stress and extreme sensitivity to expression level. Overexpression of PtsI is likely to be a useful arrow in the metabolic engineer’s quiver as productivity of engineered pathways becomes limited by central metabolic rates during stationary phase production processes.
Original languageEnglish
Article number16035
Journaln p j Systems Biology and Applications
Volume3
Issue number1
Number of pages7
ISSN2056-7189
DOIs
Publication statusAccepted/In press - 2019
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Computer Science Applications, Applied Mathematics, Modeling and Simulation, Biochemistry, Genetics and Molecular Biology (all), Drug Discovery

ID: 170362295